Microsurgical replantation after forehead avulsion - success or failure? A case report.

In this article we would like to present, to our best knowledge, the very first published replantation of a forehead/part of a forehead as a single unit. The patient is a 57-year-old male smoker who sustained an avulsion forehead injury after a dog bite. Replantation was performed using microanastomosis of the supratrochlear vessels with restoration of good blood circulation after the procedure. Unfortunately, 5 days after the surgery, ischemia of the flap occurred followed by successful acute revision surgery. Nevertheless, the day after the ischemia reoccurred due to the time that passed, circumstances and unfavorable conditions affecting the sutured vessels, no further revision surgery was indicated. Observation continued and eventual wound necrosis after demarcation was left to be treated with skin grafting or per secundam intentionem. Only partial necrosis of the flap occurred, approximately 50%, which was subsequently treated with a full-thickness skin graft with very good results leading to the satisfaction of the patient.

Head-to-head comparison of two continuous glucose monitoring systems on a cardio-surgical ICU.

In critical illness hypo-and hyperglycemia have a negative influence on patient outcome. Continuous glucose monitoring (CGM) could help in early detection of hypo-and hyperglycemia. A requirement for these new methods is an acceptable accuracy and precision in clinical practice. In this pilot study we prospectively evaluated the accuracy and precision of two CGM sensors (subcutaneous sensor: Sentrino®, Medtronic and intravasal sensor: Glucoclear®, Edwards) in 20 patients on a cardio-surgical ICU in a head to head comparison. CGM data were recorded for up to 48 h and values were compared with blood-gas-analysis (BGA) values, analysed with Bland-Altman-plots and color-coded surveillance error-grids. Shown are means ± standard deviations. In total 270/255 intravasal/subcutaneous pairs with BGA-values were analysed. The average runtime of the sensors was 28.4 ± 6.4 h. Correlation with BGA values yielded a correlation coefficient of 0.76 (subcutaneous sensor) and 0.92 (intravasal sensor). The Bland Altman Plots revealed an accuracy of 2.5 mg/dl, and a precision of + 43.0 mg/dl to - 38.0 mg/dl (subcutaneous sensor) and an accuracy of - 6.0 mg/dl, and a precision of + 12.4 mg/dl to - 24.4 mg/dl (intravasal sensor). No severe hypoglycemic event, defined as BG level below 40 mg/dl, occurred during treatment. Both sensors showed good accuracy in comparison to the BGA values, however they differ regarding precision, which in case of the subcutaneous sensor is considerable high.

Neurologic sequelae associated with delayed identification of iatrogenic skull base injury during endoscopic sinus surgery (ESS).

BACKGROUND: Skull base injury is an infrequent complication during endoscopic sinus surgery (ESS). We hypothesize that late recognition and repair of CSF leaks during ESS is associated with increased neurologic morbidity. METHODOLOGY: A retrospective review was performed of patients with skull base injury during ESS at a tertiary center from 1999-2015. The study population was separated into early (less than 72 hrs) and late (more than 72 hrs) intervention groups. Study parameters included time to diagnosis, imaging, site of injury, type of repair, neurologic complications, and clinical outcomes. RESULTS: Seventeen patients were studied. The primary surgical interventions included ESS and balloon sinuplasty. Mean latency from primary surgery to presentation to our facility was 11 days. The most common injury site was the cribriform plate and the mean defect size 4.5 mm. Late diagnosis was associated with increased total neurologic complications and increased rates of postoperative meningitis. No neurologic complications occurred in patients diagnosed intraoperatively. All patients underwent successful endoscopic repair. CONCLUSION: Skull base injury is a rare but major complication following both balloon sinuplasty and traditional primary ESS. Early diagnosis and endoscopic repair may prevent neurologic morbidity in these patients.

The potential of ki67 and p53 assessment in development of individualized targeted therapy in breast cancer patients.

INTRODUCTION: Despite the improvement of diagnostic methods and chemotherapeutic regimens in breast cancer, overall 5-year survival significantly depends on the stage of the disease. Over expression of tumor suppressor gene p53 and the marker for cellular proliferation Ki67 in breast cancer may have prognostic significance. METHODS: We evaluated 675 patients diagnosed with breast cancer at UF Health Jacksonville between January 2000 and June 2007 with up to 5-year follow up. The aim of the study was to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 may predict outcome, the 'hazard' of dying. Cox's proportional hazards models were used to control for age (< 50 vs. ≥ 50), race (white vs. other), lymph node group (negative vs. positive), ER (estrogen receptor) group (negative vs. positive), PR (progesterone receptor) group (negative vs. positive), and tumor type. RESULTS: When only p53 was considered in the model, the hazard of dying was significantly higher for p53 positive compared to p53 negative (HR = 1.32, 95% CI 1.02, 1.70, p = 0.036). When only ki67 was considered in the model, the hazard of dying was significantly higher for ki67 positive compared to ki67 negative (Hazard ratio = 1.64, 95% CI 1.08, 2.49, p = 0.021). Neither of the two markers, nor their interaction was significant when all variables were considered in the model. DISCUSSION: This study confirms the expression of p53 and Ki67 as strong individual indicators of patient outcome. However, when controlling for the other variables, the two markers are not independent predictors. Future studies that will include these markers might help design targeted therapy.

Carcinoma cuniculatum: not a verrucous carcinoma.

BACKGROUND: Carcinoma cuniculatum and verrucous carcinoma are both very well differentiated forms of squamous carcinoma and thus difficult to separate histologically from pseudocarcinomatous hyperplasia. The diagnosis of each often requires clinical-pathologic correlation. METHODS: We reviewed the literature on cases reported as carcinoma cuniculatum and compared these to the cases originally reported by Aird et al. In addition, we report an additional case of this entity that we encountered in our practice. RESULTS: In reviewing the literature it is evident that most authors consider carcinoma cuniculatum and verrucous carcinoma to be synonymous even though Aird's original two cases had no verrucous features. The lack of a clear conceptual distinction between these two entities may cause diagnostic confusion. CONCLUSION: The purpose of this report is to record a case of carcinoma cuniculatum which the authors believe to be similar to those reported by Aird et al., to emphasize the differences between carcinoma cuniculatum and verrucous carcinoma, and to explain how the lack of a clear conceptual distinction between these two tumors can lead to further delay in an already difficult diagnosis.

Technology-enhanced distance education: from experimentation to concerted action.

Despite the rush to embrace technology-enhanced learning (TEL), descriptions of how schools of nursing move toward systemwide implementation of this type of teaching are scarce. There is a wide gap between sporadic dabbling by individual instructors in specific courses and adoption and implementation of TEL throughout a program. This article describes the experiences of a group of nursing faculty who helped move one school of nursing from experimentation with TEL in distance education to concerted action toward a strategic schoolwide plan. J Prof Nurs 17:135-140, 2001.

A practical, theory-based approach to establishing school nutrition advisory councils.

This article describes a process for establishing school nutrition advisory councils (SNACs) as an integral part of a school environment approach to promoting the nutritional health of students. The application of social cognitive theory as the conceptual framework for SNACs is discussed and the steps for establishing councils, including describing the school food environment, recruiting council members and convening the council, are reviewed. Actions taken by SNACs to positively affect the school nutrition environment are also described. SNACs are 1 component of the Teens Eating for Energy and Nutrition at School (TEENS) study, a group randomized, school-based intervention trial conducted in 16 middle schools in the Minneapolis-St Paul, Minn, metropolitan area. TEENS seeks to promote healthful dietary behaviors among young adolescents to reduce future cancer risk. Primary outcome measures include increasing fruit and vegetable intake and decreasing fat consumption. SNACs were established in the intervention schools to assess the overall school food environment and to advance school-level policy that promotes a healthful food environment.

Is your financial house in order?

In today's rapidly changing world individuals are being faced by many new issues that are challenging their ability to survive financially. It is therefore important that we recognize the need to manage our financial lives. To do that requires a commitment of time to identify assets held and determine how best to protect them, set future financial goals, and then determine how assets can be used to reach those goals.

Oligonucleotide inhibitors of human thrombin that bind distinct epitopes.

Thrombin, a multifunctional serine protease, recognizes multiple macromolecular substrates and plays a key role in both procoagulant and anticoagulant functions. The substrate specificity of thrombin involves two electropositive surfaces, the fibrinogen-recognition and heparin-binding exosites. The SELEX process is a powerful combinatorial methodology for identifying high-affinity oligonucleotide ligands to any desired target. The SELEX process has been used to isolate single-stranded DNA ligands to human thrombin. Here, a 29-nucleotide single-stranded DNA ligand to human thrombin, designated 60-18[29], with a Kd of approximately 0.5 nM is described. DNA 60-18[29] inhibits thrombin-catalyzed fibrin clot formation in vitro. Previously described DNA ligands bind the fibrinogen-recognition exosite, while competition and photocrosslinking experiments indicate that the DNA ligand 60-18[29] binds the heparin-binding exosite. DNA 60-18[29] is a quadruplex/duplex with a 15-nucleotide "core" sequence that has striking similarity to previously described DNA ligands to thrombin, but binds with 20 to 50-fold higher affinity. The 15-nucleotide core sequence has eight highly conserved guanine residues and forms a G-quadruplex structure. A single nucleotide within the G-quadruplex structure can direct the DNA to a distinct epitope. Additional sequence information in the duplex regions of ligand 60-18[29] contribute to greater stability and affinity of binding to thrombin. A low-resolution model for the interaction of DNA 60-18[29] to human thrombin has been proposed.

Isolation and characterization of 2'-fluoro-, 2'-amino-, and 2'-fluoro-/amino-modified RNA ligands to human IFN-gamma that inhibit receptor binding.

CD4+ Th cells produce cytokines that play a pivotal role in the induction and regulation of cell-mediated and humoral immunity. Th1 cells, characterized by their secretion of IFN-gamma, induce macrophage cytotoxicity, delayed hypersensitivity, and enhanced cellular immunity. Secretion of IFN-gamma may even suppress Th2-enhanced humoral immunity. A counterproductive Th1 response and concomitant secretion of IFN-gamma may result in inflammatory and autoimmune diseases. IFN-gamma regulation of T cell function has potential for therapeutic intervention. To isolate high affinity oligonucleotide inhibitors of IFN-gamma activity, combinatorial libraries of RNA molecules modified at the 2' position of pyrimidine nucleotides with fluoro (F), amino (NH2), or a mixture of F and NH2 (2'-F/NH2) were screened using the SELEX (systematic evolution of ligands by exponential enrichment) combinatorial chemistry process. Each modified library of RNA molecules provides an expanded repertoire of molecules with increased structural diversity and unique binding properties. This added diversity increases the possibility of isolating molecules with the desired functional properties. These RNAs modified at the 2' position have also been shown to be nuclease resistant. High affinity ligands to human IFN-gamma from each modified library were isolated and characterized. The K(d)s of these ligands were determined and their secondary structures were predicted. The specificity of these ligands for IFN-gamma binding was confirmed, and their ability to inhibit binding of IFN-gamma to its receptor on A549 human lung carcinoma cells was determined. A 2'-NH2-modified ligand (2'-NH2-30) is described that binds IFN-gamma with high affinity and inhibits IFN-gamma-induced expression of MHC class I and ICAM-1 by human myeloid leukemia cells.

[Maternal hyperphenylalaninemia in a population of healty Czech women. 18 years' experience with mass screening, diet therapy and metabolic monitoring]. / Materské hyperfenylalaninémie v ceské populaci zdravých tehotných zen. 18leté zkusenosti s fakultativním screeningem, dietní lécbou a metabolickým sledováním.

BACKGROUND: Elevated phenylalanine levels in maternal blood (hyperphenylalaninaemia) during pregnancy damages the developing foetal tissues. Early detection of pregnant women with hyperphenylalaninaemia and adherence to a low phenylalanine diet already before conception and throughout pregnancy can prevent this damage. The objective of the investigation are results achieved screening and strict monitoring of low phenylalanine dietetic treatment in detected pregnant women of the Prague population. METHODS AND RESULTS: 186 350 healthy women of the Prague population were examined by the chromatographic screening test in a venous blood sample during their first visit in a maternity welfare centre and 22 positive cases were detected (incidence 1:8470). In 86% mild, persistent or benign forms of phenylketonuria were involved. Nineteen patients were treated by a low phenylalanine diet and the phenylalanine tolerance was monitored as well as the nitrogen balance, amino acids in serum and urine, protein markers, trace elements, vitamins, lipids, the body mass index-BMI, changes of body weight after introduction of the dietetic treatment and treatment during pregnancy. A significant increase of the phenylalanine tolerance by 20 to 200% was found, mostly in the second half of pregnancy and reduced values of serum and urinary selenium. The decrease of body weight when the diet was introduced and the increment during pregnancy correlated with the BMI value. In the other investigated parameters no significant deviations were found. CONCLUSION: Fifteen healthy children with normal psychomotor development delivered by 12 mothers with hyperphenylalaninaemia provide evidence of the effectiveness of prenatal screening for hyperphenylalaninaemia during pregnancy.

High-affinity RNA ligands to human alpha-thrombin.

Systematic Evolution of Ligands by EXponential enrichment (SELEX) was used to isolate from a population of 10(13) RNA molecules two classes of high affinity RNAs that bind specifically to human alpha-thrombin. Class I RNAs are represented by a 24-nucleotide RNA (RNA 16.24), and class II RNAs are represented by a 33-nucleotide RNA (RNA 27.33). RNA 16.24 inhibits thrombin-catalyzed fibrin clot formation in vitro. Secondary structures are proposed for these RNAs, revealing a novel stem-loop structure for RNA 16.24, comprised of an unusually large 16-nucleotide loop. Mutants of RNA 16.24 were generated to investigate structural features critical to high-affinity binding. Phosphate modification with ethylnitrosourea identified regions of the RNAs necessary for electrostatic interactions. Competition with heparin suggests that these RNAs bind the electropositive heparin-binding site of thrombin. These ligands represent a novel class of thrombin inhibitors that may be suitable for therapeutic or diagnostic applications.

Transactivation by the human T-cell leukemia virus Tax protein is mediated through enhanced binding of activating transcription factor-2 (ATF-2) ATF-2 response and cAMP element-binding protein (CREB).

The human T-cell leukemia virus type I (HTLV-I)-encoded transcriptional activator protein Tax is strongly implicated in HTLV-I pathogenesis. Tax regulates HTLV-I gene expression through three 21-base pair (bp) repeat enhancer elements located in the transcriptional control region of the virus. Tax does not bind these elements directly, but mediates transactivation through the cellular transcription factors that recognize a cAMP response element (CRE)-like sequence centered within each of the 21-bp repeats. In this report, we identify activating transcription factor-2 (ATF-2) and CRE-binding protein (CREB) as the principal T-cell proteins that bind the three 21-bp repeats in vitro. Purified Tax protein augments the level of RNA synthesis induced by ATF-2 and CREB in a cell-free transcription assay, providing evidence that Tax cooperates with these cellular proteins to activate HTLV-I transcription. Furthermore, Tax dramatically increases the binding of both the T-cell-derived and recombinant forms of ATF-2 and CREB to each of the 21-bp repeats. The target sequences for this enhancement reside within the DNA binding/dimerization domains of these proteins. These data suggest that Tax transactivates HTLV-I gene expression by increasing the number of bound ATF-2 and CREB molecules at the viral promoter.

Nifedipine and nisoldipine in hypertensive diabetics.

The effects of nisoldipine and slow release nifedipine on mild to moderate hypertension and glycaemic control were studied in 28 diabetic hypertensives, all except one of whom were non-insulin dependent. After two weeks placebo treatment patients were randomised to receive either nisoldipine 5 mg twice daily or nifedipine 10 mg twice daily. If, after four weeks of treatment, diastolic blood pressures (DBP) were 95 mmHg or more, the doses were doubled. On the 'optimum' dose patients were reviewed at weeks 4, 8, 12 and 24. At each visit blood was taken for haematology, biochemistry, glucose and glycosylated haemoglobin (GHb). Twenty-four hour home blood glucose (HBG) profiles were done at the end of the placebo period, and at weeks 8, 12, and 24, when on 'optimum' treatment. Mean sitting blood pressure fell from 173/99 to 161/92 (nisoldipine) and 158/86 mmHg (nifedipine) on the lower doses. Responses to higher doses were less marked. Changes in post breakfast blood glucose and GHb were not statistically significant. There were no significant changes in 24 hr HBG profiles on nisoldipine 5 mg and only minor decreases on 10 mg. On nifedipine 10 mg there was a similar change but on 20 mg an increase in HBG was seen at all points.

BK virus and JC virus shed during pregnancy have predominantly archetypal regulatory regions.

Twenty-three BK virus and JC virus DNA samples obtained from urine of pregnant women had almost exclusively archetypal transcriptional control regions. Rearrangements characteristic of laboratory strains are apparently not required for reactivation in humans. Unexpectedly, alignment shows that many elements identified previously in the BK virus enhancer are conserved in the JC virus archetype.

Nedocromil sodium in adults with asthma dependent on inhaled corticosteroids: a double blind, placebo controlled study.

Eighty nine adults with asthma who were receiving inhaled corticosteroid and bronchodilator treatment took part in a double blind, randomised, placebo controlled trial of nedocromil sodium, 4 mg four times daily by inhalation. During a run in period of two to four weeks corticosteroid treatment was reduced when possible to produce a comparable level of symptoms across the trial population. The test treatment was then taken for four weeks, with the severity of asthma recorded daily by patients and assessed at two weekly hospital visits. There was an improvement in symptoms in the patients taking nedocromil sodium by comparison with those having the placebo, the differences being significant for diary card PEF readings, asthma symptom scores, and bronchodilator usage at night. The mean difference between the two groups was 18 l/min for PEF, 0.42 for daytime asthma score, and 1.73 puffs in 24 hours for bronchodilator usage. These results suggest that asthmatic patients who require inhaled steroids show better control of their asthma with the addition of nedocromil sodium than of placebo over a four week period after reduction of the dosage of their inhaled steroids.

A serial study of platelet reactivity throughout the first six months after myocardial infarction: its modification by sulphinpyrazone.

Platelet reactivity was studied immediately after and throughout the first 6 months following myocardial infarction. Its modification by sulphinpyrazone was observed. Out of 65 consecutive patients admitted to the coronary care unit, ten did not meet the protocol criteria. Fifty five received either placebo or sulphinpyrazone in a double-blind trial for 6 months, treatment being started within 6 days of infarction. Forty four patients completed the study (19 on placebo and 25 on sulphinpyrazone). An additional ten patients commenced treatment within one day of infarction and were studied daily for one week. Platelet hyper-reactivity was demonstrable in all patients at presentation and persisted throughout the 6 months in the control group. This effect was reversed by sulphinpyrazone, the modification of reactivity being established by the third day of treatment.